During development of and following injury to the nervous system, the growth and regeneration of axons is strongly influenced by astrocyte-derived extracellular matrix molecules (Silver & Miller (2004) Nat. Rev. Neurosci. 5:146-156) and Schwann cell-derived basement membrane molecules (Chernousov & Carey (2000) Histol. Histopathol. 15:593-601). The basement membrane is a structurally compact form of the extracellular matrix. Examples of such molecules include thrombospondin in the extracellular matrix (Adams & Tucker (2000) Dev. Dyn. 218:280-299) and laminin-1 in the basement membrane (Chernousov & Carey (2000) supra). In this regard, the extracellular matrix produced by astrocytes includes both positive (e.g., thrombospondin, fibronectin) and negative (e.g., chondroitin and keratan sulphate proteoglycans) effectors of neuronal growth (Lein (1992) Brain Res. Dev. Brain Res. 69:191-197; Kearns, et al. (2003) Exp. Neurol. 182:240-244; Silver (1994) J. Neurol. 242:S22-4; Silver & Miller (2004) supra).
Electrospun nanofibers have been suggested as providing a scaffold that mimics the extracellular matrix (Li, et al. (2002) J. Biomed. Mater. Res. A 60:613-621). Nanofibers produced via the process of electrospinning have unprecedented porosity, a high surface to volume ratio, and high interconnectivity, all physical properties that are ideal for cellular attachment and growth (Li, et al. (2002) supra). The nanofiber aggregates can be deposited in either a random or aligned array, to result in random or oriented axonal growth (Yang, et al. (2005) Biomaterial 26:2603-2610). Nanofibers electrospun from a variety of synthetic and naturally occurring polymers have generated tremendous interest due to their potential as scaffolds for regenerating tissue (Kidoaki, et al. (2005) Biomater. 26:37-46; Ma, et al. (2005) Tissue Eng. 11:1149-1158; Venugopal & Ramakrishna (2005) Appl. Biochem. Biotechnol. 125:147-158; Schindler, et al. (2006) Cell Biochem. Biophys. 45:215-228), with a recent study indicating that silk nanofibers improved bone regeneration in the rabbit (Kim, et al. (2005) J. Biotechnol. 120:327-339).
Tenascin-C, a multi-domain, multi-functional extracellular matrix glycoprotein with neuro-regulatory actions (Gotz, et al. (1996) J. Cell Biol. 132:681-699; Dorries, et al. (1996) J. Neurosci. Res. 43:420-438; Meiners & Geller (1997) Mol. Cell Neurosci. 10:100-116; Meiners & Mercado (2003) Molec. Neurobiol. 27:177-196; Meiners, et al. (2001) J. Neurosci. 21:7215-7225) has also been shown to provide a chemical cue that might enhance the function of a nanofibrillar scaffold. Research has also focused on the growth-promoting actions of the alternatively spliced fibronectin type III region of human tenascin-C. The active site for neurite outgrowth in this region was localized from cerebellar granule, cerebral cortical, spinal cord motor, and dorsal root ganglion neurons to a peptide with amino acid sequence Val-Phe-Asp-Asn-Phe-Val-Leu-Lys-Ile-Arg-Asp-Thr-Lys-Lys (SEQ ID NO: 1) (Meiners, et al. (2001) supra; Ahmed, et al. (2006) J. Biomed Mater. Res. A 76:851-860), called the D5 peptide. It was recently demonstrated that covalent modification of electrospun polyamide nanofibers with the D5 peptide promoted more in vivo-like growth patterns for neurons, with long, well elaborated processes (Ahmed, et al. (2006) supra).
Moreover, chitosan nanofibers modified with bone morphogenetic protein-2 enhanced adhesion and proliferation of and calcium deposition by osteoblastic cells; the effect on adhesion was dose-dependant with the amount of bone morphogenetic protein-2 attached to the nanofiber surface (Park, et al. (2006) Biotehnol. Appl. Biochem. 43:17-24). Furthermore, derivatization of poly(caprolactone) nanofibers with gelatin increased endothelial cell proliferation and allowed the cells to maintain their expression of platelet-endothelial cell adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in culture (Ma, et al. (2005) supra).